Skin cancer stands as a challenging global health concern, necessitating innovative approaches to cure deficiencies within traditional therapeutic modalities. While conventional drug delivery methods through injection or oral administration have long prevailed, the emergence of topical drug administration presents a compelling alternative. The skin, aside from offering a swift and painless procedure, serves as a reservoir, maintaining drug efficacy over extended durations. This comprehensive review seeks to shed light on the potential of nanotechnology as a promising avenue for efficacious cancer treatment, with a particular emphasis on skin cancer. Additionally, it underscores the transdermal approach as a viable strategy for addressing various types of cancer. This work also explores into the delivery of peptides and proteins along with in-depth explanations of different delivery systems currently under investigation for localized skin cancer treatment. Furthermore, the review discusses the formidable challenges that must be surmounted before these innovations can find their way into clinical practice, offering a roadmap for future research and therapeutic development.